Social Network Characteristics Associated with More Frequent HIV and STI Prevention Conversations: The N2 Cohort Study in Chicago.

Black cisgender sexually minoritized men (SMM) and transgender women (TW) are subgroups at highest risk of HIV and sexually transmitted infections (STIs) in the US. We sought to identify factors facilitating continued conversations - social reinforcement - surrounding HIV/STI prevention among this subgroup. Participants were recruited in Chicago from 2018 to 2019 from community health spaces. Participants provided information about themselves (level 2) and ⩽5 confidants (level 1). We used multinomial multilevel modeling to identify associations with HIV/STI prevention conversation frequency. A total of 370 participants provided information on 987 confidants (mean = 2.6). We found significantly positive associations between having biweekly or more often HIV/STI prevention conversations and a confidant being a kin family member, older by 15 years or more, racially homophilous, and emotionally close. Future interventions should harness social networks by including components that consider racial homophily, respect for elders, and strong ties, in addition to applying kin family systems interventions approaches and decreasing stigma surrounding HIV/STIs.

Lyme disease and post-treatment Lyme disease syndrome: the neglected disease in our own backyard.

OBJECTIVES: A survey was developed to assess experience and opinions about Lyme disease and post-treatment Lyme disease syndrome (PTLDS) among faculties in public health. No previous surveys of public health faculties have been found in the literature. STUDY DESIGN: This is a cross sectional study of public health school faculty members designed to measure knowledge and experience with Lyme disease and PTLDS using an internet survey instrument. METHODS: Participants were recruited using all the publicly available e-mail addresses of faculty members in all the 50 accredited Schools of Public Health in the United States. RESULTS: A 15% response rate was seen for the survey. 50% of respondents were from Lyme endemic states. Less than 5% of faculty members consider themselves expert in Lyme or PTLDS. Many faculty members had known someone with Lyme disease or PTLDS, but few had been diagnosed themselves. Most believe that PTLDS can be severe and chronic, is not easy to treat, and does not resolve on its own, but were uncertain about its aetiology. Most respondents also felt that the incidence of Lyme disease will increase and that more education is needed. CONCLUSIONS: The need for further understanding and communication presents an opportunity for public health research and education in Lyme disease and the sequelae of PTLDS.

Noninvasive determination of 2-[18F]-fluoroisonicotinic acid hydrazide pharmacokinetics by positron emission tomography in Mycobacterium tuberculosis-infected mice.

Tuberculosis (TB) is a global pandemic requiring sustained therapy to facilitate curing and to prevent the emergence of drug resistance. There are few adequate tools to evaluate drug dynamics within infected tissues in vivo. In this report, we evaluated a fluorinated analog of isoniazid (INH), 2-[(18)F]fluoroisonicotinic acid hydrazide (2-[(18)F]-INH), as a probe for imaging Mycobacterium tuberculosis-infected mice by dynamic positron emission tomography (PET). We developed a tail vein catheter system to safely deliver drugs to M. tuberculosis aerosol-infected mice inside sealed biocontainment devices. Imaging was rapid and noninvasive, and it could simultaneously visualize multiple tissues. Dynamic PET imaging demonstrated that 2-[(18)F]-INH was extensively distributed and rapidly accumulated at the sites of infection, including necrotic pulmonary TB lesions. Compared to uninfected animals, M. tuberculosis-infected mice had a significantly higher PET signal within the lungs (P < 0.05) despite similar PET activity in the liver (P > 0.85), suggesting that 2-[(18)F]-INH accumulated at the site of the pulmonary infection. Furthermore, our data indicated that similar to INH, 2-[(18)F]-INH required specific activation and accumulated within the bacterium. Pathogen-specific metabolism makes positron-emitting INH analogs attractive candidates for development into imaging probes with the potential to both detect bacteria and yield pharmacokinetic data in situ. Since PET imaging is currently used clinically, this approach could be translated from preclinical studies to use in humans.

On the emerging role of rabbit as human disease model and the instrumental role of novel transgenic tools.

The laboratory rabbit (Oryctolagus cuniculus) is widely used as a model for human diseases, because of its size, which permits non-lethal monitoring of physiological changes and similar disease characteristics. Novel transgenic tools such as, the zinc finger nuclease method and the sleeping beauty transposon mediated or BAC transgenesis were recently adapted to the laboratory rabbit and opened new opportunities in precise tissue and developmental stage specific gene expression/silencing, coupled with increased transgenic efficiencies. Many facets of human development and diseases cannot be investigated in rodents. This is especially true for early prenatal development, its long-lasting effects on health and complex disorders, and some economically important diseases such as atherosclerosis or cardiovascular diseases. The first transgenic rabbits models of arrhythmogenesis mimic human cardiac diseases much better than transgenic mice and hereby underline the importance of non-mouse models. Another emerging field is epigenetic reprogramming and pathogenic mechanisms in diabetic pregnancy, where rabbit models are indispensable. Beyond that rabbit is used for decades as major source of polyclonal antibodies and recently in monoclonal antibody production. Alteration of its genome to increase the efficiency and value of the antibodies by humanization of the immunoglobulin genes, or by increasing the expression of a special receptor (Fc receptor) that augments humoral immune response is a current demand.

Provision of trauma care in asymmetric warfare: a conceptual framework to support the decision to implement frontline care services.

INTRODUCTION: The emerging trends of asymmetric and urban warfare call for a revision of the needs and the way in which frontline trauma care is provided to affected population. However, there is no consensus on the process to decide when and how to provide such lifesaving interventions in form of Trauma Stabilization Point (TSP). METHODS: A three-step Delphi method was used to establish consensus. A focus group discussion was convened to propose a framework and develop the list of twenty-one (21) statements for validation of a group of experts. RESULTS: A panel of twenty-eight (28) experts reviewed the statements and participated to both first and second rounds. Comments and recommendations provided by the FGD and during round 1 were used to analyze the findings of the study. The proposed framework includes five main categories identified as interconnected components that facilitate the decision to implement or not the TSP. A total of sixteen (16) elements distributed across the five categories have been considered as being able to guide the decision to utilize such capability in high-risk security and resource constrained settings. CONCLUSION: The TSP has the potential to prevent death and disability. The proposed framework and categories add a structure to the decision-making process and represents an important step to support emergency and trauma care planning and implementation efforts.

Neu differentiation factor (NDF), a dominant oncogene, causes apoptosis in vitro and in vivo.

Neu differentiation factor (NDF, also called neuregulin) is a potent inducer of epithelial cell proliferation and has been shown to induce mammary carcinomas in transgenic mice. Notwithstanding this proliferative effect, we have shown that a novel isoform of NDF can induce apoptosis when overexpressed. Here we report that this property also extends to other NDF isoforms and that the cytoplasmic portion of NDF is largely responsible for the apoptotic effect, whereas the proliferative activity is likely to depend upon the secreted version of NDF. In accordance with these contradictory properties, we find that tumors induced by NDF display extensive apoptosis in vivo. NDF is therefore an oncogene whose deregulation can induce transformation as well as apoptosis.

An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans.

Two small temporal RNAs (stRNAs), lin-4 and let-7, control developmental timing in Caenorhabditis elegans. We find that these two regulatory RNAs are members of a large class of 21- to 24-nucleotide noncoding RNAs, called microRNAs (miRNAs). We report on 55 previously unknown miRNAs in C. elegans. The miRNAs have diverse expression patterns during development: a let-7 paralog is temporally coexpressed with let-7; miRNAs encoded in a single genomic cluster are coexpressed during embryogenesis; and still other miRNAs are expressed constitutively throughout development. Potential orthologs of several of these miRNA genes were identified in Drosophila and human genomes. The abundance of these tiny RNAs, their expression patterns, and their evolutionary conservation imply that, as a class, miRNAs have broad regulatory functions in animals.

The importance of aerobic metabolism in the renal concentrating process.

The extent to which the concentrating function of the kidney depends on oxidative processes was investigated by infusing cyanide into one renal artery of dogs undergoing mild mannitol diuresis while receiving an infusion of vasopressin. This produced an abrupt fall in concentrating capacity (T(c) (H2O)) that was reversed when the cyanide infusion was stopped. The change could not be accounted for by the accompanying solute diuresis, since it was not reproduced by increasing the rate of mannitol infusion. The reduction in T(c) (H2O) induced by cyanide did not result from increased delivery of dilute urine to the collecting ducts, since free water clearance (C(H2O)), studied in other dogs during water diuresis, was unchanged or decreased by cyanide. Cyanide produced renal vasodilatation, as did intraarterial acetylcholine, but in contrast to the striking reduction in concentrating capacity evoked by cyanide, T(c) (H2O) was not significantly changed by acetylcholine. The data indicate that concentrating ability is closely tied to oxidative metabolism in the kidney, and it is suggested that the region where this is critically important is the red medulla and the thick ascending limb of Henle's loop.

The extracellular region of heregulin is sufficient to promote mammary gland proliferation and tumorigenesis but not apoptosis.

Heregulin (HRG) is a member of the neuregulin family of ligands that have been shown to interact with and activate erbB receptors. A transgenic mouse model in which full-length HRG is overexpressed has proven that this protein can induce carcinomas in the murine mammary gland. These tumors display a high level of apoptosis, which appears to be mediated by the cytoplasmic domain of HRG. Because both proliferation and apoptosis play a role in tumor formation, we wished to separately view those perturbations by removing the suspected apoptosis-inducing cytoplasmic domain of HRG. We thereby sought to determine whether overexpression of the extracellular region of HRG would be sufficient to induce mammary gland carcinomas. A HRG construct lacking the cytoplasmic domain was targeted to the mammary gland using the murine mammary tumor virus promoter. Multiple lines of transgenic mice carrying the transgene developed mammary gland tumors at approximately 15 months of age. These tumors did not display high levels of apoptosis as compared with tumors from murine mammary tumor virus/full-length HRG transgenic animals. In addition, virgin transgenic mice show a persistence of terminal end bud structures, which normally disappear at the onset of puberty in wild-type mice. To examine the signal transduction pathway activated by extracellular HRG in tumors, we investigated the phosphorylation status of the epidermal growth factor receptor family members. Western blot analysis showed activation of ErbB2 and ErbB3, suggesting a possible mode of action of extracellular HRG in mammary gland carcinomas. We conclude that the extracellular and transmembrane domains of HRG are sufficient for the induction of tumorigenesis but that induction of apoptosis requires the cytoplasmic tail.

The oncogene heregulin induces apoptosis in breast epithelial cells and tumors.

The products of a growing number of genes have been shown to display seemingly contradictory functions; namely, the induction of tumorigenesis and the induction of apoptosis. Heregulin's involvement in oncogenesis occurs through its interactions with members of the EGF receptor tyrosine kinase family. Recently one isoform of heregulin, beta2b, was isolated in an in vitro screen for dominant, apoptosis-inducing genes in kidney epithelial cells. Here we show that heregulin is also capable of mediating apoptosis in human and murine mammary tumor cell lines and murine tumors. Furthermore, through transfection of the human breast cancer cell line MCF-7 with the truncated transmembrane/cytoplasmic segment of the heregulin gene, we show that the intracellular region of the heregulin precursor is sufficient for induction of apoptosis. Through the use of DNA fragmentation assays we also show that apoptosis occurs in cell lines established from heregulin-induced mammary gland tumors. TdT addition of digoxigenin labeled nucleotides to 3' OH ends of DNA breaks recapitulated these results in the actual tumors. Finally, over-expression of heregulin is shown to lead to the down-regulation of Bcl-2, an inhibitor of apoptosis. Conversely, the transfection of Bcl-2 into MCF-7 cells inhibits heregulin-mediated programmed cell death.

Two-dimensional and Doppler echocardiography alone can adequately define preoperative anatomy and hemodynamic status before repair of complete atrioventricular septal defect in infants < 1 year old.

OBJECTIVES: We sought to assess the ability of two-dimensional and Doppler echocardiography alone, without cardiac catheterization, to evaluate infants < 1 year of age for complete open heart repair of complete balanced atrioventricular (AV) septal defect. BACKGROUND: Two-dimensional echocardiographic-Doppler examinations provide accurate anatomic detail in patients with AV septal defect. Lung biopsy data have shown that patients rarely develop significant inoperable pulmonary vascular disease before 7 months of age. Although calculated pulmonary arteriolar resistance is often elevated in young infants with this heart defect, this elevation rarely reflects significant pulmonary vascular changes in infants < 7 to 12 months of age. METHODS: We performed a retrospective review of 34 patients who underwent complete repair of AV septal defect at our institution between January 1, 1988 and September 1, 1992. Some patients had both catheterization and echocardiographic-Doppler studies (group I, n = 16); others had only echocardiographic-Doppler studies (group II, n = 18). RESULTS: The groups were comparable with regard to age at echocardiography and operation, days in the hospital, days with ventilatory and inotropic support and occurrence of postoperative pulmonary hypertension. One child (2.9%) died during the early postoperative period, and one child in each group (5.8%) died within the 1st year of life. Preoperative echocardiography allowed better detailing of anatomy, valve commitment and regurgitation than was possible with catheterization alone. Knowledge of preoperative pulmonary resistance did not alter the surgical decision or predict postoperative pulmonary hypertension. There was no apparent difference in mortality between the two groups (0 vs. 5.5%), but the small number of patients in each group provides for a very low power (beta = 0.04) calculation. This mortality rate is not different from that reported in recent studies. CONCLUSIONS: Patients with AV septal defect can safely undergo surgical correction of this defect on the basis of echocardiographic-Doppler data alone.

Abnormal brain glucose metabolism in the delusional misidentification syndromes: a positron emission tomography study in Alzheimer disease.

Brain lesions have been reported with increasing frequency in the delusional misidentification syndromes (DMS). This is the first controlled study to describe DMS regional cerebral metabolic rates of glucose (rCMRglc). We compared rCMRglc (using positron emission tomography) and neuropsychological data in 9 patients with DMS and Alzheimer dementia (AD), 15 AD patients without DMS, and 17 healthy controls. The DMS group differed from the AD group without DMS in having significant hypometabolism in paralimbic (orbitofrontal and cingulate areas bilaterally) and left medial temporal areas, and significant bilateral normalized hypermetabolism in sensory association cortices (superior temporal and inferior parietal) without right left asymmetry. Compared to healthy controls, both AD groups had significant dorso lateral frontal hypometabolism bilaterally. No specific DMS neuropsychological profile was identified. Dysfunctional connections among multimodal association areas, paralimbic structures, and dorsolateral frontal cortex are proposed as the predisposing neural deficit underlying DMS, causing cognitive-perceptual-affective dissonance, which under specific conditions results in "positive" delusion formation.

Usefulness of Doppler echocardiography in diagnosing right ventricular coronary arterial communications in patients with pulmonary atresia and intact ventricular septum and comparison with angiography.

Direct and indirect evidence of right ventricular coronary arterial communications has been detected by use of 2-dimensional and Doppler echocardiography in patients with pulmonary atresia and intact ventricular septum. We describe additional consistent and reproducible Doppler echocardiographic findings that were useful for identifying patients in whom abnormal coronary arterial flow patterns were detected angiographically.

Fetal echocardiography. A tool for evaluation of in utero cardiac arrhythmias and monitoring of in utero therapy: analysis of 71 patients.

Fetal echocardiographic studies were performed in 71 patients referred for evaluation of cardiac rhythm disturbances at 24 to 40 weeks' gestation. After 2-dimensional echocardiographic study of cardiac structure was performed, M-mode echocardiograms were analyzed for measurement of cardiac rate, atrioventricular contraction sequence, atrioventricular valve motion, and duration of postectopic pauses. Arrhythmias were diagnosed in 59 patients. In 34 patients with isolated ectopic beats, the arrhythmia resolved during later pregnancy in 26 or within the first 5 days of life in 8. Six patients had mild sinus bradycardia and 8 had frequent sinus pauses; all 14 had resolution of the arrhythmia during pregnancy. Sustained arrhythmias occurred in 11 patients. Deaths occurred when there was associated fetal congestive heart failure (hydrops fetalis), structural heart disease, or both. M-mode echocardiography diagnosed supraventricular tachycardia in 3 fetuses. The echocardiogram was used thereafter for monitoring transplacental digoxin therapy.

Isolation and identification of 1alpha-hydroxy-24-oxovitamin D3 and 1alpha,23-dihydroxy-24-oxovitamin D3: metabolites of 1alpha,24(R)-dihydroxyvitamin D3 produced in rat kidney.

1alpha,24(R)-Dihydroxyvitamin D3 [1alpha,24(R)(OH)2D3], a synthetic vitamin D3 analog, has been developed as a drug for topical use in the treatment of psoriasis. At present, the target tissue metabolism of 1alpha,24(R)(OH)2D3 is not understood completely. In our present study, we investigated the metabolism of 1alpha,24(R)(OH)2D3 in the isolated perfused rat kidney. The results indicated that 1alpha,24(R)(OH)2D3 is metabolized in rat kidney into several metabolites, of which 1alpha,24(R),25-trihydroxyvitamin D3, 1alpha,25-dihydroxy-24-oxovitamin D3, 1alpha,23(S),25-trihydroxy-24-oxovitamin D3, and 1alpha,23-dihydroxy-24,25,26,27-tetranorvitamin D3 are similar to the previously known metabolites of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3]. In addition to these aforementioned metabolites, we also identified two new metabolites, namely 1alpha-hydroxy-24-oxovitamin D3 and 1alpha,23-dihydroxy-24-oxovitamin D3. The two new metabolites do not possess the C-25 hydroxyl group. Thus, the metabolism of 1alpha,24(R)(OH)2D3 into both 25-hydroxylated and non-25-hydroxylated metabolites suggests that 1alpha,24(R)(OH)2D3 is metabolized in the rat kidney through two pathways. The first pathway is initiated by C-25 hydroxylation and proceeds further via the C-24 oxidation pathway. The second pathway directly proceeds via the C-24 oxidation pathway without prior hydroxylation at the C-25 position. Furthermore, we demonstrated that rat kidney did not convert 1alpha-hydroxyvitamin D3 [1alpha(OH)D3] into 1alpha,25(OH)2D3. This finding indicates that the rat kidney does not possess the classical vitamin D3-25-hydroxylase (CYP27) activity. However, from our present study it is apparent that prior hydroxylation of 1alpha(OH)D3 at the C-24 position in the 'R' orientation allows 25-hydroxylation to occur. At present, the enzyme responsible for the C-25 hydroxylation of 1alpha,24(R)(OH)2D3 is unknown. Our observation that the side chain of 1alpha,24(R)(OH)2D3 underwent 24-ketonization and 23-hydroxylation even in the absence of the C-25 hydroxyl group suggests that 1alpha,25(OH)2D3-24-hydroxylase (CYP24) can perform some steps of the C-24 oxidation pathway without prior C-25 hydroxylation. Thus, we speculate that CYP24 may be playing a dual role in the metabolism of 1alpha,24(R)(OH)2D3.

Nucleolar localization of BRCA1 protein in human breast cancer.

Both a rabbit polyclonal BRCA1 antibody, K-18, and a mouse monoclonal BRCA1 antibody, AP 16, produced nucleolar epithelial cell staining on frozen tissue sections of human infiltrating mammary carcinomas. There was much less BRCA1 antibody staining in normal tissues; however, 2 intraductal tumors and a papilloma, found in proximity to the carcinomas showed considerable nucleolar immunoreactivity. MCF-7 cells fixed in methanol and immunostained with the same two antibodies also revealed nucleolar staining, however, after 4% paraformaldehyde fixation for three minutes, there were many fewer nuclei stained. Antigen retrieval methods on formalin-fixed, paraffin-embedded specimens produced tumor cell cytoplasmic staining with AP 16 and nuclear staining in both tumor and normal epithelial cells with another BRCA1 monoclonal antibody, SG 11.

Mitral atresia with premature closure of foramen ovale. A rare hemodynamic cause for failure of Blalock-Taussig anastomosis to relieve inadequate pulmonary blood flow.

The clinical, hemodynamic, and surgical findings encountered in the management of a hypoxic male infant with a rare and complex variety of cyanotic congenital heart disease associated with inadequate pulmonary blood flow are described. A poor clinical response to creation of a Blalock-Taussig anastomosis led to the discovery of mitral atresia complicated by premature closure of the foramen ovale and partially relieved by the presence of a levoatriocardinal vein. The subsequent creation of an atrial septal defect enhanced the function of the subclavian artery to pulmonary artery anastomosis and provided palliative relief of hypoxia. Some of the clinical and laboratory findings indicating the presence of additional lesions complicating the picture of a tetralogy of Fallot and requiring additional surgical considerations are discussed. The experience indicates that hemodynamic as well as surgical causes may explain the failure of a systemic artery to pulmonary artery anastomosis to function adequately and should be sought.

Hyperinflation of the lungs in infants with large left-to-right shunts.

Infants with significant left-to-right shunts due to ventricular septal defects and atrioventricular canal defects commonly present with respiratory symptoms, such as shortness of breath while feeding, tachypnea, and wheezing. Radiographs show hyperinflated lungs as well as cardiomegaly and increased vascularity. Enlarged vessels adjacent to small compressible airways as well as peribronchial interstitial edema may cause diffuse air trapping. In this study, using an automated planimetric device, we measured the total thoracic, cardiomediastinal, and lung volumes in a group of patients with large left-to-right shunts as well as in a group of normal controls and found that, as expected, all volumes were significantly increased in the abnormal group. We also tried to correlate these volumes (corrected for patient size) with the degree of left-to-right shunt and found that there was no significant correlation between the cardiac or lung volumes and shunt size as estimated by cardiac catheterization.

Paraesophageal hiatus hernia in the aged.

A review of the records of Granada Hills Hospital revealed 4 documented cases of paraesophageal hiatus hernia. One of these geriatric patients presented with incarceration of the gastric fundus, and required an emergency thoracotomy for relief. Paraesophageal hiatus hernia, unlike sliding hiatal hernia, often gives rise to acute surgical problems secondary to incarceration, obstruction, gangrene, perforation or hemorrhage. The approach to the repair operation, may be either abdominal or thoracic, dependent upon the need to correct other associated gastrointestinal pathologic lesions. Unless severe debilitating medical diseases are present, operative intervention is recommended.

Experimental myocardial ischemia. Differential injury of mitochondrial subpopulations.

Distinct populations of subsarcolemmal (SS) and inter-fibrillar (IF) rat cardiac mitochondria were studied following 15 and 30 minutes of warm and cold global ischemia. The respiratory control index, state 3, state 4, adenosine diphosphate-oxygen ratio, and specific enzyme activities of these mitochondrial populations were examined. The subsarcolemmar and IF mitochondria were both severely uncoupled and inhibited by warm ischemia. However, IF mitochondria had a higher RCI at each ischemic interval. In cold ischemia, IF mitochondria were not injured compared with control specimens. Subsarcolemmar mitochondria showed a trend towards a lower RCI that was statistically significant at 30 minutes with succinate as a substrate. These data implicate a differential injury of ischemia on the compartmentalized bioenergy metabolism of the myocardial cell.